Development of a supported liquid membrane process for separating enantiomers of N-protected amino acid derivatives
Development of a supported liquid membrane process for separating enantiomers of N-protected amino acid derivatives
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DOI：
10.1016/j.memsci.2005.09.050
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发表时间：
2006-05
影响因子：
9.5
通讯作者：
A. Maximini;H. Chmiel;H. Holdik;N. Maier
中科院分区：
文献类型：
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作者：
A. Maximini;H. Chmiel;H. Holdik;N. Maier
开发了一种连续支撑液膜 (SLM) 工艺，利用高选择性氨甲酰化奎宁和奎尼丁衍生物作为载体时提供的优势，分离外消旋 N-保护氨基酸衍生物的对映体。该工艺的特点是两种对映体都可以以99%的纯度进行大量分离（以克为单位）。 SLM 工厂的原型基本上由两个中空纤维膜组件组成，其中包含 250 根聚砜中空纤维，膜总表面积为 0.1 平方米，截留分子量为 30kD。孔中的液膜由金刚烷基-氨基甲酰基-11-十八烷基硫醚-奎宁（模块1）和奎尼丁（模块2）组成，其溶解在1-癸醇/十五烷中。对映选择性分离过程在水相中连续进行。基于外消旋体的氨基酸衍生物 DNB-d,l-亮氨酸、DNZ-Tle、DNZ-ABA 和 DNZ-β-Phe 可以在 SLM 设备中分离，选择性程度在 2 到 4 之间。通过向载体添加 5vol.% 聚硅氧烷键合的奎宁/奎尼丁聚合物，可以防止偶尔观察到的膜上结晶。此外，可以保证提高对机械影响（浸出）的抵抗力。使用模型物质DNB-d,l-亮氨酸来测试该过程。经过五个分离步骤后，可以产生 99% 的 d-对映体和 99% 的 l-对映体，跨膜通量超过 20mmol/m2h。可以证明，与类似的工业规模手性技术相比，SLM 技术可以提供高水平的生产率和灵活性。
A continuous supported liquid membrane (SLM) process was developed to separate enantiomers of racemic N-protected amino acid derivatives using the advantages provided by highly selective carbamoylised quinine and quinidine derivatives when used as a carrier. The special characteristic of this process is that both enantiomers can be separated with degree of purity of 99% and in large quantities (in grams). The prototype of a SLM plant consisted basically of two hollow fibre membrane modules with 250 individual polysulfone hollow fibres, a total membrane surface of 0.1m2and a molecular weight cut-off of 30kD. The liquid membrane in the pores consisted of adamantyl-carbamoyl-11-octadecylthioether-quinine (module 1) and -quinidine (module 2), which was dissolved in 1-decanole/pentadecane. The enantioselective separation process operates on a continuous basis in aqueous phases. The amino acid derivatives DNB-d,l-leucine, DNZ-Tle, DNZ-ABA and DNZ-β-Phe based on the racemate could be separated in the SLM plant with a degree of selectivity between 2 and 4. Crystallisation on the membrane, which is occasionally observed was prevented by adding a 5vol.% polysiloxane-bonded quinine/quinidine polymer to the carrier. Furthermore, improved resistance to mechanical influences (leaching) could be guaranteed. The model substance DNB-d,l-leucine was used to test the process. After five separation steps, a 99% d-enantiomer and a 99% l-enantiomer could be produced at a transmembrane flux of more than 20mmol/m2h. It could be shown that SLM technology can offer a high level of productivity and flexibility compared to analogous industrial-scale chiral technologies.